Psychopharmacology Lecture Nodes
Lecture 1. Introduction
Psychopharmacology in general
Psychopharmacology is the field that studies the effect of substances on behaviour, cognition and
affect, including their mechanisms on the brain.
There is some controversion about the use of psychopharmaca due to undesirable side effects.
Psychopharmacology can be of importance in finding the balance between the benefits as well as the
side effects of a drug, including on the long term.
Psychokinetics = what does the body do to the substance (how does a substance move through the
body)
Psychodynamics = what does the substance do to the body (what kind of effect does it have,
interactions with neurotransmitter systems)
Biological psychology basis
There are a lot of neurotransmitters and neurons in the brain, but there a relatively few number of
neurons that react to a specific type of neurotransmitter. Therefore, they are really specific targets
for drugs, which makes it more difficult. On the other hand you also have drugs that influence
neurotransmitters that are present in a lot of neurons in the body. Problems with this specificity of
drug targets can lead to the occurrence of undesirable effects because of the stimulation of
unintended synapses.
Neurotransmitters come from precursors. Precursors are monoamines that you get through your
food, that contain the essential pieces for creating a neurotransmitter, for example tyrosine is the
precursor of dopamine, noradrenaline and adrenaline.
Neurotransmitters act in the synapse. There are different locations where receptors can be located:
• Post-synaptic receptor
• Pre-synaptic receptor
→ Autoreceptors that detect the release of own neuron or groups of neurons that use the
same neurotransmitter, to regulate the further release of neurotransmitter
→ Heteroreceptor is localized on the presynaptic neuron of one synapse, but it is affected by
another neuron.
After neurotransmission the released neurotransmitters are being removed, by degradation
(metabolism) in the synapse and reuptake within the presynaptic cell.
Most drugs affect synaptic transmission by effecting receptors, which can influence transmitter
production, transmitter release or transmitter clearance. See figure 4.10 on slides for detailed
information.
The basis for knowledge on psychopharmacology
In psychopharmacology most of the first insights or later developments of drugs came from
serendipity. However, intentionally hypothesis-based research on drugs is preferred.
Hypothesis are based on:
1) Basic knowledge → preclinical research: appliance of substances on animals
2) Clinical knowledge → clinical research: appliance of substances to clinical populations
,I. Preclinical phases (animal research)
• Efficacy
• Administration → Does substance pass through blood-brain barrier or survive gastro-intestinal
system
• Safety → Therapeutic index, drug interactions, toxicity (expected and unexpected side effects)
Therapeutic index (TI) = relationship between the toxic dose (TD) and the effective dose (ED). A
bigger distance between TD and ED curve is preferable, because you can more easily choose a dose
in which there is a therapeutic effect, but the toxic effects are not or barely present.
TI is calculated by dividing the dose where 50% of the people experiences the toxic effect (TI) by the
dose where 50% of the people experience the therapeutic effect. TI should ideally be a large number
to be a safe drug.
II. Clinical trials (human research)
• Phase 1: non-toxic, tolerable → administration of the drug in small group of healthy people
• Phase 2: limited efficacy studies → starts with open labeled research in a small clinical
population in which the researcher as well as the participant knows who gets the drug and who
doesn’t (cost-benefit consideration).
• Phase 3: large, multi-center studies → not only studying whether the new drug is effective, but
also if it is better than existing drugs.
• Phase 4: monitoring after introduction → registering side effects that people report
Different names of a drug:
- Chemical name/formula
- Codename
- Generic name
- Brand name
Medicine is a drug that aims to cure, while a drug does not necessarily have that purpose. In other
words: all medicines are drugs, but not all drugs are medicines.
Optimal dose is the dose where there is a maximum effect with as little side effects as possible.
Medicines are registered for certain indications or groups, but sometimes a physician prescribes
medicine for another indication or group = off label use.
Lecture 2. Principles of psychopharmacology
Why use psychoactive substances? Why psychopharmacology?
Psychoactive substances are substances that influence behavior, if taken effectively, by effecting the
brain.
We use psychopharmacology to:
- Understand the effect of substances on behavior
- To clinically improve behavior by optimizing application of psychoactive substances
- Manipulate behavior via psychoactive substances to understand behavior, by its effect on brain
and neurotransmitters.
How much of psychoactive substances? - Dose and dosage
When we want to say something about the dose of a given substance, we look at a graph where the
dose (x-axis) is presented against the blood-concentration (y-axis).
, On the other hand, you can get information about a dose by looking at a dose-response curve (DRC),
which represents response as a function of dose
To create a DRC, you need a clear representation of an increasing dose of a substance (x-axis) and an
output parameter for the response (y-axis). The curve really depends on which response you look at.
A DRC can vary from individual to individual and therefore should be estimated, because a DRC is the
on average response across a group of people for given doses of a certain substance.
Terms of a DRC (see slide to see where in de curve it is located)
• Potency = minimum dose for a noticeable effect (minimum dose lower → potency is higher)
• Efficacy = the maximum effect that a drug can have on a specific output parameter
• Expected effect of a given dose
→ Dependent on the ease with which the substance crosses the blood-brain barrier.
Increasing a dose can come with undesirable effects, so called side effects, because of the increasing
stimulance of other processes other than the intended.
The DRC of the desired effect should essentially be to the left of the undesired effect.
You should choose a dose within the therapeutic window, which gives a range of how strong you
want the desired effect to be versus how strong you can tolerate the undesired effect to be. So, how
much of the side-effect is acceptable given the required effect. This can be very different per
individual.
Why do you want to know how they work? How do they work? – Pharmacodynamics
Pharmacodynamics is about signaling in/between cells and how this is influenced by drugs. It’s about
the biochemical and physiological effects of substances. In a synapse there are multiple targets that
drugs can influence.
You want to know how they work to:
• To relieve symptoms and reduce side-effects. If you know what drugs actually do at the level of
neurons, you might come up with ideas how this trade-off can be improved.
• To stop an addiction, like smoking by understanding the working mechanism of a substance, e.g.
nicotine.
High affinity of substance → binding potential of radioactive will be low (receptors already occupied)
Low affinity of substance → binding potential of radioactive will by high (receptors not occupied)
There is a relationship between the potency of a drug and its affinity: high affinity = high potency &
low affinity = low potency. If that is the case, it becomes likely that the clinical effect of a drug is
dependent on their affinity for a target receptor. (See slides for example haloperidol).
If a substance is intended to target certain receptors in a specific part of the brain, it might be the
case that these receptors are also present in other parts of the brain of the body. This can cause the
undesirable side effects of a substance.
Example haloperidol:
- Haloperidol (antipsychotic) has high affinity for dopamine-2 receptor, it binds easily.
- Haloperidol is relatively potent, a relatively low dose is enough for an antipsychotic effect.
- Haloperidol blocks this receptor, so the efficacy is 0 (full antagonist).
- But the DAD2 receptor is also located in other parts of the brain, in which the blockade causes
undesirable side effects, like motor problems.
